I’m finishing my PhD project, which I analysed high grade serous ovarian carcinoma on patients with different clinical responses to carboplatin using transcriptome and I found MMP14 differentially expressed. On protein analysis, higher levels of MMP14 immunostaining were associated with better prognosis (OS and PFS survival analysis). I’m struggling to understand how MMP14 could initiate intraperitoneal metastases, with initial detachment of tumour spheroids from the surface of the ovary (Lengyel 2010) and at the meantime, be a protective factor of better prognosis in high grade serous ovarian carcinoma.
Have someone a hypothesis to share about this?
Hi Mariana, these are very interesting results!.
I have not worked with MMP14, but I have worked with MMP9 and MMP2. For these MMPs, TIMPs play a major role in controlling their activities.
I have not been active in this field, but a paragraph in
http://cancerres.aacrjournals.org/content/63/23/8511.long
caught my eye:
"Others have since demonstrated that MMP-14, a protein anchored to the cell membrane of stromal cells, binds to TIMP-2 through its catalytic domain and then uses it as a receptor for pro-MMP-2, a protein also initially produced by the stromal cells. Free adjacent MMP-14 can then cleave the Asn37-Leu38 bond of pro-MMP-2 leading to MMP-2 intermolecular autocatalytic cleavage of the Asn80-Tyr81 bond. This process leads to an active and soluble form of MMP-2 called MMP-2a. MMP-2a can then bind to cancer cells via an αvβ3 integrin (7 , 26 , 43)"
If this holds up, then high MMP-14 and low TIMP-2 will not activate other MMPs, leading to less invasive properties.
Hope this helps.
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